scholarly journals MEF2A Regulates the MEG3-DIO3 miRNA Mega Cluster-Targeted PP2A Signaling in Bovine Skeletal Myoblast Differentiation

2019 ◽  
Vol 20 (11) ◽  
pp. 2748 ◽  
Author(s):  
Yaning Wang ◽  
Chugang Mei ◽  
Xiaotong Su ◽  
Hongbao Wang ◽  
Wucai Yang ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Molecular Mechanisms ◽  
Regulatory Subunit ◽  
Myoblast Differentiation ◽  
Mirna Cluster ◽  
Skeletal Myoblast ◽  
Iodothyronine Deiodinase ◽  
Luciferase Activity Assay ◽  
Phosphatase 2A ◽  
Protein Phosphatase 2

Understanding the molecular mechanisms of skeletal myoblast differentiation is essential for studying muscle developmental biology. In our previous study, we reported that knockdown of myocyte enhancer factor 2A (MEF2A) inhibited myoblast differentiation. Here in this study, we further identified that MEF2A controlled this process through regulating the maternally expressed 3 (MEG3)—iodothyronine deiodinase 3 (DIO3) miRNA mega cluster and protein phosphatase 2A (PP2A) signaling. MEF2A was sufficient to induce MEG3 expression in bovine skeletal myoblasts. A subset of miRNAs in the MEG3-DIO3 miRNA cluster was predicted to target PP2A subunit genes. Consistent with these observations, MEF2A regulated PP2A signaling through its subunit gene protein phosphatase 2 regulatory subunit B, gamma (PPP2R2C) during bovine myoblast differentiation. MiR-758 and miR-543 in the MEG3-DIO3 miRNA cluster were down-regulated in MEF2A-depleted myocytes. Expression of miR-758 and miR-543 promoted myoblast differentiation and repressed PPP2R2C expression. Luciferase activity assay showed that PPP2R2C was post-transcriptionally targeted by miR-758 and miR-543. Taken together, these results reveal that the MEG3-DIO3 miRNAs function at downstream of MEF2A to modulate PP2A signaling in bovine myoblast differentiation.

scholarly journals Protein Phosphatase 2A Subunit PR70 Interacts with pRb and Mediates Its Dephosphorylation

2007 ◽  
Vol 28 (2) ◽  
pp. 873-882 ◽  
Author(s):  
Alessandra Magenta ◽  
Pasquale Fasanaro ◽  
Sveva Romani ◽  
Valeria Di Stefano ◽  
Maurizio C. Capogrossi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Phosphatase ◽  
Molecular Mechanisms ◽  
Protein Phosphatase 2A ◽  
Phosphate Removal ◽  
Regulatory Subunit ◽  
Phosphatase 2A ◽  
Retinoblastoma Tumor

ABSTRACT The retinoblastoma tumor suppressor protein (pRb) regulates cell proliferation and differentiation via phosphorylation-sensitive interactions with specific targets. While the role of cyclin/cyclin-dependent kinase complexes in the modulation of pRb phosphorylation has been extensively studied, relatively little is known about the molecular mechanisms regulating phosphate removal by phosphatases. Protein phosphatase 2A (PP2A) is constituted by a core dimer bearing catalytic activity and one variable B regulatory subunit conferring target specificity and subcellular localization. We previously demonstrated that PP2A core dimer binds pRb and dephosphorylates pRb upon oxidative stress. In the present study, we identified a specific PP2A-B subunit, PR70, that was associated with pRb both in vitro and in vivo. PR70 overexpression caused pRb dephosphorylation; conversely, PR70 knockdown prevented both pRb dephosphorylation and DNA synthesis inhibition induced by oxidative stress. Moreover, we found that intracellular Ca2+ mobilization was necessary and sufficient to trigger pRb dephosphorylation and PP2A phosphatase activity of PR70 was Ca2+ induced. These data underline the importance of PR70-Ca2+ interaction in the signal transduction mechanisms triggered by redox imbalance and leading to pRb dephosphorylation.

scholarly journals PP2A-B55 promotes nuclear envelope reformation after mitosis in Drosophila

2018 ◽  
Vol 217 (12) ◽  
pp. 4106-4123 ◽  
Author(s):  
Haytham Mehsen ◽  
Vincent Boudreau ◽  
Damien Garrido ◽  
Mohammed Bourouh ◽  
Myreille Larouche ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Envelope ◽  
Protein Phosphatase ◽  
Molecular Mechanisms ◽  
Mitotic Exit ◽  
Regulatory Subunit ◽  
Mechanistic Studies ◽  
Daughter Cells ◽  
Phosphatase 2A ◽  
Drosophila Cells

As a dividing cell exits mitosis and daughter cells enter interphase, many proteins must be dephosphorylated. The protein phosphatase 2A (PP2A) with its B55 regulatory subunit plays a crucial role in this transition, but the identity of its substrates and how their dephosphorylation promotes mitotic exit are largely unknown. We conducted a maternal-effect screen in Drosophila melanogaster to identify genes that function with PP2A-B55/Tws in the cell cycle. We found that eggs that receive reduced levels of Tws and of components of the nuclear envelope (NE) often fail development, concomitant with NE defects following meiosis and in syncytial mitoses. Our mechanistic studies using Drosophila cells indicate that PP2A-Tws promotes nuclear envelope reformation (NER) during mitotic exit by dephosphorylating BAF and suggests that PP2A-Tws targets additional NE components, including Lamin and Nup107. This work establishes Drosophila as a powerful model to further dissect the molecular mechanisms of NER and suggests additional roles of PP2A-Tws in the completion of meiosis and mitosis.

scholarly journals Regulatory Subunit B′γ of Protein Phosphatase 2A Prevents Unnecessary Defense Reactions under Low Light in Arabidopsis

2011 ◽  
Vol 156 (3) ◽  
pp. 1464-1480 ◽  
Author(s):  
Andrea Trotta ◽  
Michael Wrzaczek ◽  
Judith Scharte ◽  
Mikko Tikkanen ◽  
Grzegorz Konert ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunit ◽  
Low Light ◽  
Defense Reactions ◽  
Phosphatase 2A ◽  
Subunit B

scholarly journals Protein Phosphatase 2A Regulatory Subunit B56α Associates with c-Myc and Negatively Regulates c-Myc Accumulation

2006 ◽  
Vol 26 (7) ◽  
pp. 2832-2844 ◽  
Author(s):  
Hugh K. Arnold ◽  
Rosalie C. Sears
Keyword(s):  
Tumor Suppressor ◽  
Protein Phosphatase ◽  
Cell Function ◽  
Cell Transformation ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunit ◽  
Suppressor Activity ◽  
Tumor Suppressor Activity ◽  
Structural Subunit ◽  
Phosphatase 2A

ABSTRACT Protein phosphatase 2A (PP2A) plays a prominent role in controlling accumulation of the proto-oncoprotein c-Myc. PP2A mediates its effects on c-Myc by dephosphorylating a conserved residue that normally stabilizes c-Myc, and in this way, PP2A enhances c-Myc ubiquitin-mediated degradation. Stringent regulation of c-Myc levels is essential for normal cell function, as c-Myc overexpression can lead to cell transformation. Conversely, PP2A has tumor suppressor activity. Uncovering relevant PP2A holoenzymes for a particular target has been limited by the fact that cellular PP2A represents a large heterogeneous population of trimeric holoenzymes, composed of a conserved catalytic subunit and a structural subunit along with a variable regulatory subunit which directs the holoenzyme to a specific target. We now report the identification of a specific PP2A regulatory subunit, B56α, that selectively associates with the N terminus of c-Myc. B56α directs intact PP2A holoenzymes to c-Myc, resulting in a dramatic reduction in c-Myc levels. Inhibition of PP2A-B56α holoenzymes, using small hairpin RNA to knock down B56α, results in c-Myc overexpression, elevated levels of c-Myc serine 62 phosphorylation, and increased c-Myc function. These results uncover a new protein involved in regulating c-Myc expression and reveal a critical interconnection between a potent oncoprotein, c-Myc, and a well-documented tumor suppressor, PP2A.

scholarly journals Cdc55p, the B-type regulatory subunit of protein phosphatase 2A, has multiple functions in mitosis and is required for the kinetochore/spindle checkpoint in Saccharomyces cerevisiae.

1997 ◽  
Vol 17 (2) ◽  
pp. 620-626 ◽  
Author(s):  
Y Wang ◽  
D J Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Phosphatase ◽  
Elevated Temperatures ◽  
Protein Phosphatase 2A ◽  
Spindle Checkpoint ◽  
Mitotic Checkpoint ◽  
Regulatory Subunit ◽  
Phosphatase 2A ◽  
A Subunit ◽  
Normal Sensitivity

Saccharomyces cerevisiae, like most eucaryotic cells, can prevent the onset of anaphase until chromosomes are properly aligned on the mitotic spindle. We determined that Cdc55p (regulatory B subunit of protein phosphatase 2A [PP2A]) is required for the kinetochore/spindle checkpoint regulatory pathway in yeast. ctf13 cdc55 double mutants could not maintain a ctf13-induced mitotic delay, as determined by antitubulin staining and levels of histone H1 kinase activity. In addition, cdc55::LEU2 mutants and tpd3::LEU2 mutants (regulatory A subunit of PP2A) were nocodazole sensitive and exhibited the phenotypes of previously identified kinetochore/spindle checkpoint mutants. Inactivating CDC55 did not simply bypass the arrest that results from inhibiting ubiquitin-dependent proteolysis because cdc16-1 cdc55::LEU2 and cdc23-1 cdc55::LEU2 double mutants arrested normally at elevated temperatures. CDC55 is specific for the kinetochore/spindle checkpoint because cdc55 mutants showed normal sensitivity to gamma radiation and hydroxyurea. The conditional lethality and the abnormal cellular morphogenesis of cdc55::LEU2 were suppressed by cdc28F19, suggesting that the cdc55 phenotypes are dependent on the phosphorylation state of Cdc28p. In contrast, the nocodazole sensitivity of cdc55::LEU2 was not suppressed by cdc28F19. Therefore, the mitotic checkpoint activity of CDC55 (and TPD3) is independent of regulated phosphorylation of Cdc28p. Finally, cdc55::LEU2 suppresses the temperature sensitivity of cdc20-1, suggesting additional roles for CDC55 in mitosis.

scholarly journals Molecular Mechanisms Underlying Cardiac Protein Phosphatase 2A Regulation in Heart

2012 ◽  
Vol 288 (2) ◽  
pp. 1032-1046 ◽  
Author(s):  
Sean T. DeGrande ◽  
Sean C. Little ◽  
Derek J. Nixon ◽  
Patrick Wright ◽  
Jedidiah Snyder ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Molecular Mechanisms ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A
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